The compound 5-(hydroxymethyl)furfural (HMF) is an important intermediate substance readily made from renewable resources, specifically carbohydrates.
HMF is a suitable molecule for the formation of various furan ring derivatives that are known intermediates for certain chemical syntheses, and as potential substitutes for benzene based derivatives ordinarily derived from petroleum resources. Due to its various functionalities, it has been proposed that HMF could be utilized to produce a wide range of products such as polymers, solvents, surfactants, pharmaceuticals, and plant protection agents. As substitutes, one may compare derivatives of HMF to chemicals with the corresponding benzene-based rings or to other compounds containing a furan or tetrahydrofuran. HMF and 2,5-disubstituted furans and tetrahydrofuran derivatives, therefore, have great potential in the field of intermediate chemicals from renewable agricultural resources. In order to compete with petroleum based derivatives, however, preparation of HMF derivatives from common agricultural source materials, such as sugars, must be economical.
One of the concerns with HMF, is that it has limited uses as a chemical per se, other than as a source for making derivatives. Furthermore, HMF itself is rather unstable and tends to polymerize and or oxidize with prolonged storage. Due to the instability and limited applications of HMF itself, studies have broadened to include the synthesis and purification of a variety of HMF derivatives. Two derivatives of particular interest include the reduced HMF forms furan-2,5-dimethanol (FDM) and 2,5-bis-(hydroxymethyl)tetrahydrofuran (THF-diol).
These derivatives have been successfully synthesized in two steps involving the dehydration of fructose to HMF, followed by purification, and subsequent hydrogenation of the purified HMF (see U.S. Pat. No. 7,317,116). Studies have shown HMF, however, that as mentioned above, HMF itself is unstable and is also somewhat difficult to isolate. It would be useful to find a route to synthesis FDM, THF-diol and ether derivatives that did not require the intermediate step of purifying HMF.
Other derivatives of recent interest include HMF secondary and tertiary amines. This class of compounds is useful, for example, as a building block for pharmaceuticals such as ranitidine or Zantac™, which is a well known antiulcer drug. The traditional synthetic route for making ranitidine is according to the following series of reactions:
The fourth compound in this reaction sequence is the HMF derivative 5′-[(dimethylamino)methyl]furfuryl alcohol, which is ordinarily made by reacting 2-hydroxymethyl furan with dimethylamine and formaldehyde as shown in the first line above. The method requires 3 steps to obtain the HMF amine derivative and the use of two hazardous chemicals, dimethylamine and formaldehyde. Dimethylamine is ranked as one of the most the most hazardous compounds (worst 10%) to ecosystems and human health. Formaldehyde also poses health risks with a recommended airborne exposure limit of 0.75 ppm averaged over an 8-hour work shift by the National Institute for Occupational Safety and Health. The National Institute for Occupational Safety and Health's currently sets the short-term exposure limit at 0.1 ppm for 15 minutes. Methods which do not expose humans and the environment to these toxic chemicals are desired for large scale production.
Other furanic secondary and tertiary amines compounds that can be derived from HMF are useful for other purposes, for example, resins, surfactants, and antimicrobial agents. Accordingly, there is a need in the art for efficient and cost effective methods to make furandimethanol, HMF ethers and furanic alkylamino derivatives from inexpensive and less hazardous starting materials.